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Although microRNAs are supposed to be stable in-vivo , degradation processes potentially blur our knowledge on the small oligonucleotides. We set to quantify the effect of degradation on microRNAs in mouse to identify causes for distorted microRNAs patterns. In liver, we found 298, 99 and 8 microRNAs whose expression significantly correlated to RNA integrity, storage time at room temperature and storage time at 4 °C, respectively. Expression levels of 226 microRNAs significantly differed between liver samples with high RNA integrity compared to liver samples with low RNA integrity by more than two-fold. Especially the 157 microRNAs with increased expression in tissue samples with low RNA integrity were most recently added to miRBase. Testing potentially confounding sources, e.g. in-vitro degraded RNA depleted of small RNAs, we detected signals for 350 microRNAs, suggesting cross-hybridization of fragmented RNAs. Therefore, we conclude that especially microRNAs added in the latest miRBase versions might be artefacts due to RNA degradation. The results facilitate differentiation between degradation-resilient microRNAs, degradation-sensitive microRNAs, and likely erroneously annotated microRNAs. The latter were largely identified by NGS but not experimentally validated and can severely bias microRNA biomarker research and impact the value of microRNAs as diagnostic, prognostic or therapeutic tools.

ICOS-Oceans is the marine domain of the European Research Infrastructure Consortium “Integrated Carbon Observation System” (ICOS). It aims at delivering high quality greenhouse gas (GHG) observations and derived data products (e.g. regional GHG-flux maps) for constraining the GHG balance on a European level, on a sustained long-term basis. ICOS-Oceans currently consists of 11 Ship of Opportunity lines (SOOP – Ship of Opportunity Program) and 10 Fixed Observation Stations (FOS) spread across European waters, including the North Atlantic Ocean and the Barents, North, Baltic and Mediterranean Seas. The stations operate in a harmonised and standardised way based on community-proven protocols and methods for ocean GHG observations improving operational conformity as well as quality control and assurance of the data. This enables the network to focus on long term research into the marine carbon cycle and the anthropogenic carbon sink, while preparing the network to include other GHG fluxes. ICOS data are processed on a near real-time basis and will be published on the ICOS Carbon Portal, allowing monthly estimates of CO2 air-sea exchange to be quantified for European waters. ICOS establishes transparent operational data management routines following the FAIR (Findable, Accessible, Interoperable and Reusable) guiding principles allowing amongst others reproducibility, interoperability and traceability. The ICOS-Oceans network is actively integrating with the atmospheric (e.g. improved atmospheric measurements onboard SOOP lines) and ecosystem (e.g. oceanic direct gas flux measurements) domains of ICOS, and utilises techniques developed by the ICOS Central Facilities and the Carbon Portal. There is a strong interaction with the international ocean carbon cycle community to enhance interoperability and harmonise data flow. The future vision of ICOS-Oceans includes ship-based ocean survey sections to obtain a 3-dimensional understanding of marine carbon cycle processes and optimise the existing network design.

Background: We sought to determine the diagnostic performance of the new high-sensitivity cardiac troponin T (hs-cTnT) assay for early detection of non–ST-segment myocardial infarction (NSTEMI) in patients with acute coronary syndrome. Methods: We enrolled patients with retrospectively confirmed unstable angina or NSTEMI and an initially negative cTnT concentration and compared the performance of baseline concentrations and serial changes in concentration within 3 and 6 h. Percentage change criteria included ≥20% δ change and ROC-optimized value. Results: Based on the standard fourth-generation cTnT result of ≥0.03 μg/L, an evolving NSTEMI was diagnosed in 26 patients, and 31 patients were classified as having unstable angina. With the use of the hs-cTnT assay at the 99th-percentile cutoff, the percentage of NSTEMI cases detected increased gradually from 61.5% on presentation to 100% within 6 h, and the overall number of MI diagnoses increased by 34.6% (35 vs 26 cases). A δ change ≥20% or ≥ROC-optimized value of >117% within 3 h or ≥243% within 6 h yielded a specificity of 100% at sensitivities between 69% and 76%. The standard cTnT at the 99th percentile was less sensitive than hs-cTnT for early diagnosis of MI on presentation, and follow-up samples obtained within the initial 3 h demonstrated very low specificity of cTnT compared with hs-cTnT. Conclusions: The high-sensitivity cTnT assay increases the number of NSTEMI diagnoses and enables earlier detection of evolving NSTEMI. A doubling of the hs-cTnT concentration within 3 h in the presence of a second concentration ≥99th percentile is associated with a positive predictive value of 100% and a negative predictive value of 88%.

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based fCO2 products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. Additional lines of evidence on land and ocean sinks are provided by atmospheric inversions, atmospheric oxygen measurements, and Earth system models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and incomplete understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2022, EFOS increased by 0.9 % relative to 2021, with fossil emissions at 9.9±0.5 Gt C yr−1 (10.2±0.5 Gt C yr−1 when the cement carbonation sink is not included), and ELUC was 1.2±0.7 Gt C yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 11.1±0.8 Gt C yr−1 (40.7±3.2 Gt CO2 yr−1). Also, for 2022, GATM was 4.6±0.2 Gt C yr−1 (2.18±0.1 ppm yr−1; ppm denotes parts per million), SOCEAN was 2.8±0.4 Gt C yr−1, and SLAND was 3.8±0.8 Gt C yr−1, with a BIM of −0.1 Gt C yr−1 (i.e. total estimated sources marginally too low or sinks marginally too high). The global atmospheric CO2 concentration averaged over 2022 reached 417.1±0.1 ppm. Preliminary data for 2023 suggest an increase in EFOS relative to 2022 of +1.1 % (0.0 % to 2.1 %) globally and atmospheric CO2 concentration reaching 419.3 ppm, 51 % above the pre-industrial level (around 278 ppm in 1750). Overall, the mean of and trend in the components of the global carbon budget are consistently estimated over the period 1959–2022, with a near-zero overall budget imbalance, although discrepancies of up to around 1 Gt C yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows the following: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living-data update documents changes in methods and data sets applied to this most recent global carbon budget as well as evolving community understanding of the global carbon cycle. The data presented in this work are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023).

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodologies to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based data products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2021, EFOS increased by 5.1 % relative to 2020, with fossil emissions at 10.1 ± 0.5 GtC yr−1 (9.9 ± 0.5 GtC yr−1 when the cement carbonation sink is included), and ELUC was 1.1 ± 0.7 GtC yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 10.9 ± 0.8 GtC yr−1 (40.0 ± 2.9 GtCO2). Also, for 2021, GATM was 5.2 ± 0.2 GtC yr−1 (2.5 ± 0.1 ppm yr−1), SOCEAN was 2.9  ± 0.4 GtC yr−1, and SLAND was 3.5 ± 0.9 GtC yr−1, with a BIM of −0.6 GtC yr−1 (i.e. the total estimated sources were too low or sinks were too high). The global atmospheric CO2 concentration averaged over 2021 reached 414.71 ± 0.1 ppm. Preliminary data for 2022 suggest an increase in EFOS relative to 2021 of +1.0 % (0.1 % to 1.9 %) globally and atmospheric CO2 concentration reaching 417.2 ppm, more than 50 % above pre-industrial levels (around 278 ppm). Overall, the mean and trend in the components of the global carbon budget are consistently estimated over the period 1959–2021, but discrepancies of up to 1 GtC yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows (1) a persistent large uncertainty in the estimate of land-use change emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extratropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living data update documents changes in the methods and data sets used in this new global carbon budget and the progress in understanding of the global carbon cycle compared with previous publications of this data set. The data presented in this work are available at https://doi.org/10.18160/GCP-2022 (Friedlingstein et al., 2022b).

We developed a simple method to refine existing open-ocean maps and extend them towards different coastal seas. Using a multi-linear regression we produced monthly maps of surface ocean fCO.sub.2 in the northern European coastal seas (the North Sea, the Baltic Sea, the Norwegian Coast and the Barents Sea) covering a time period from 1998 to 2016. A comparison with gridded Surface Ocean CO.sub.2 Atlas (SOCAT) v5 data revealed mean biases and standard deviations of 0 ± 26 µatm in the North Sea, 0 ± 16 µatm along the Norwegian Coast, 0 ± 19 µatm in the Barents Sea and 2 ± 42 µatm in the Baltic Sea. We used these maps to investigate trends in fCO.sub.2, pH and air-sea CO.sub.2 flux. The surface ocean fCO.sub.2 trends are smaller than the atmospheric trend in most of the studied regions. The only exception to this is the western part of the North Sea, where sea surface fCO.sub.2 increases by 2 µatm yr.sup.-1, which is similar to the atmospheric trend. The Baltic Sea does not show a significant trend. Here, the variability was much larger than the expected trends. Consistently, the pH trends were smaller than expected for an increase in fCO.sub.2 in pace with the rise of atmospheric CO.sub.2 levels. The calculated air-sea CO.sub.2 fluxes revealed that most regions were net sinks for CO.sub.2 . Only the southern North Sea and the Baltic Sea emitted CO.sub.2 to the atmosphere. Especially in the northern regions the sink strength increased during the studied period.

We developed a simple method to refine existing open-ocean maps and extend them towards different coastal seas. Using a multi-linear regression we produced monthly maps of surface ocean fCO2 in the northern European coastal seas (the North Sea, the Baltic Sea, the Norwegian Coast and the Barents Sea) covering a time period from 1998 to 2016. A comparison with gridded Surface Ocean CO2 Atlas (SOCAT) v5 data revealed mean biases and standard deviations of 0 ± 26 µatm in the North Sea, 0 ± 16 µatm along the Norwegian Coast, 0 ± 19 µatm in the Barents Sea and 2 ± 42 µatm in the Baltic Sea. We used these maps to investigate trends in fCO2, pH and air–sea CO2 flux. The surface ocean fCO2 trends are smaller than the atmospheric trend in most of the studied regions. The only exception to this is the western part of the North Sea, where sea surface fCO2 increases by 2 µatm yr−1, which is similar to the atmospheric trend. The Baltic Sea does not show a significant trend. Here, the variability was much larger than the expected trends. Consistently, the pH trends were smaller than expected for an increase in fCO2 in pace with the rise of atmospheric CO2 levels. The calculated air–sea CO2 fluxes revealed that most regions were net sinks for CO2. Only the southern North Sea and the Baltic Sea emitted CO2 to the atmosphere. Especially in the northern regions the sink strength increased during the studied period.

We developed a simple method to refine existing open-ocean maps and extend them towards different coastal seas. Using a multi-linear regression we produced monthly maps of surface ocean fCO2 in the northern European coastal seas (the North Sea, the Baltic Sea, the Norwegian Coast and the Barents Sea) covering a time period from 1998 to 2016. A comparison with gridded Surface OceanCO2 Atlas (SOCAT) v5 data revealed mean biases and standard deviations of 0 ± 26 µatm in the North Sea, 0 ± 16 µatm along the Norwegian Coast, 0 ± 19 µatm in the Barents Sea and 2 ± 42 µatm in the Baltic Sea. We used these maps to investigate trends in fCO2, pH and air–seaCO2 flux. The surface ocean fCO2 trends are smaller than the atmospheric trend in most of the studied regions. The only exception to this is the western part of the North Sea, where sea surface fCO2 increases by 2 µatmyr-1, which is similar to the atmospheric trend. The Baltic Sea does not show a significant trend. Here, the variability was much larger than the expected trends. Consistently, the pH trends were smaller than expected for an increase in fCO2 in pace with the rise of atmosphericCO2 levels. The calculated air–sea CO2 fluxes revealed that most regions were net sinks for CO2. Only the southern North Sea and the Baltic Sea emitted CO2 to the atmosphere. Especially in the northern regions the sink strength increased during the studied period.

Shelf seas play an important role in the global carbon cycle, absorbing atmospheric carbon dioxide (CO 2 ) and exporting carbon (C) to the open ocean and sediments. The magnitude of these processes is poorly constrained, because observations are typically interpolated over multiple years. Here, we used 298500 observations of CO 2 fugacity (fCO 2 ) from a single year (2015), to estimate the net influx of atmospheric CO 2 as 26.2 ± 4.7 Tg C yr −1 over the open NW European shelf. CO 2 influx from the atmosphere was dominated by influx during winter as a consequence of high winds, despite a smaller, thermally-driven, air-sea fCO 2 gradient compared to the larger, biologically-driven summer gradient. In order to understand this climate regulation service, we constructed a carbon-budget supplemented by data from the literature, where the NW European shelf is treated as a box with carbon entering and leaving the box. This budget showed that net C-burial was a small sink of 1.3 ± 3.1 Tg C yr −1 , while CO 2 efflux from estuaries to the atmosphere, removed the majority of river C-inputs. In contrast, the input from the Baltic Sea likely contributes to net export via the continental shelf pump and advection (34.4 ± 6.0 Tg C yr −1 ).

Quantification of land surface–atmosphere fluxes of carbon dioxide (CO2) and their trends and uncertainties is essential for monitoring progress of the EU27+UK bloc as it strives to meet ambitious targets determined by both international agreements and internal regulation. This study provides a consolidated synthesis of fossil sources (CO2 fossil) and natural (including formally managed ecosystems) sources and sinks over land (CO2 land) using bottom-up (BU) and top-down (TD) approaches for the European Union and United Kingdom (EU27+UK), updating earlier syntheses (Petrescu et al., 2020, 2021). Given the wide scope of the work and the variety of approaches involved, this study aims to answer essential questions identified in the previous syntheses and understand the differences between datasets, particularly for poorly characterized fluxes from managed and unmanaged ecosystems. The work integrates updated emission inventory data, process-based model results, data-driven categorical model results, and inverse modeling estimates, extending the previous period 1990–2018 to the year 2020 to the extent possible. BU and TD products are compared with the European national greenhouse gas inventory (NGHGI) reported by parties including the year 2019 under the United Nations Framework Convention on Climate Change (UNFCCC). The uncertainties of the EU27+UK NGHGI were evaluated using the standard deviation reported by the EU member states following the guidelines of the Intergovernmental Panel on Climate Change (IPCC) and harmonized by gap-filling procedures. Variation in estimates produced with other methods, such as atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), originate from within-model uncertainty related to parameterization as well as structural differences between models. By comparing the NGHGI with other approaches, key sources of differences between estimates arise primarily in activities. System boundaries and emission categories create differences in CO2 fossil datasets, while different land use definitions for reporting emissions from land use, land use change, and forestry (LULUCF) activities result in differences for CO2 land. The latter has important consequences for atmospheric inversions, leading to inversions reporting stronger sinks in vegetation and soils than are reported by the NGHGI.For CO2 fossil emissions, after harmonizing estimates based on common activities and selecting the most recent year available for all datasets, the UNFCCC NGHGI for the EU27+UK accounts for 926 ± 13 Tg C yr-1, while eight other BU sources report a mean value of 948 [937,961] Tg C yr-1 (25th, 75th percentiles). The sole top-down inversion of fossil emissions currently available accounts for 875 Tg C in this same year, a value outside the uncertainty of both the NGHGI and bottom-up ensemble estimates and for which uncertainty estimates are not currently available. For the net CO2 land fluxes, during the most recent 5-year period including the NGHGI estimates, the NGHGI accounted for -91 ± 32 Tg C yr-1, while six other BU approaches reported a mean sink of -62 [-117,-49] Tg C yr-1, and a 15-member ensemble of dynamic global vegetation models (DGVMs) reported -69 [-152,-5] Tg C yr-1. The 5-year mean of three TD regional ensembles combined with one non-ensemble inversion of -73 Tg C yr-1 has a slightly smaller spread (0th–100th percentiles of [-135,+45] Tg C yr-1), and it was calculated after removing net land–atmosphere CO2 fluxes caused by lateral transport of carbon (crop trade, wood trade, river transport, and net uptake from inland water bodies), resulting in increased agreement with the NGHGI and bottom-up approaches. Results at the category level (Forest Land, Cropland, Grassland) generally show good agreement between the NGHGI and category-specific models, but results for DGVMs are mixed. Overall, for both CO2 fossil and net CO2 land fluxes, we find that current independent approaches are consistent with the NGHGI at the scale of the EU27+UK. We conclude that CO2 emissions from fossil sources have decreased over the past 30 years in the EU27+UK, while land fluxes are relatively stable: positive or negative trends larger (smaller) than 0.07 (-0.61) Tg C yr-2 can be ruled out for the NGHGI. In addition, a gap on the order of 1000 Tg C yr-1 between CO2 fossil emissions and net CO2 uptake by the land exists regardless of the type of approach (NGHGI, TD, BU), falling well outside all available estimates of uncertainties. However, uncertainties in top-down approaches to estimate CO2 fossil emissions remain uncharacterized and are likely substantial, in addition to known uncertainties in top-down estimates of the land fluxes. The data used to plot the figures are available at 10.5281/zenodo.8148461 (McGrath et al., 2023).